Abstract

L1210 leukemia cells will be mixed with normal murine marrow cells and treated in vitro with deoxycoformycin in combination with Ara-A or with deoxyadenosine. These agents are cytotoxic in vitro for L1210 leukemia cells and for human leukemia cells and appear to be less toxic for hematologic stem cells. The treated marrows will be tested for their ability to reconstitute the hematologic systems of lethally irradiated mice. The long term survival of mice indicates survival of hematologic stem cells and effective purging of leukemic cells from marrow. Biochemical parameters through which deoxycoformycin exerts its cytotoxic effects will be monitored. The relevance of the biochemical sequelae of pharmacologic treatment to leukemia-free marrow engraftment will be evaluated. This is a promising model for purging marrow of leukemic cells. The application of this technique to human leukemia may make autologous bone marrow transplantation an effective treatment of leukemia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA000967-03
Application #
3079435
Study Section
(SRC)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Lin, Liyong; Solberg, Timothy D; Carabe, Alexandro et al. (2014) Pencil beam scanning dosimetry for large animal irradiation. J Radiat Res 55:855-61
Sanzari, Jenine K; Wan, Steven X; Diffenderfer, Eric S et al. (2014) Relative biological effectiveness of simulated solar particle event proton radiation to induce acute hematological change in the porcine model. J Radiat Res 55:228-44
Diffenderfer, Eric S; Dolney, Derek; Schaettler, Maximilian et al. (2014) Monte Carlo modeling in CT-based geometries: dosimetry for biological modeling experiments with particle beam radiation. J Radiat Res 55:364-72
Sanzari, J K; Wan, X S; Wroe, A J et al. (2013) Acute hematological effects of solar particle event proton radiation in the porcine model. Radiat Res 180:7-16
Sanzari, J K; Wambi, C; Lewis-Wambi, J S et al. (2011) Antioxidant dietary supplementation in mice exposed to proton radiation attenuates expression of programmed cell death-associated genes. Radiat Res 175:650-6
Sheridan, J F; Tutschka, P J; Sedmak, D D et al. (1990) Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic bone marrow transplantation. Blood 75:1583-6
Copelan, E A; Kapoor, N; Berliner, M et al. (1989) Bone marrow transplantation without total-body irradiation in patients aged 40 and older. Transplantation 48:65-8
Copelan, E A; Johnson, S C; Grever, M R et al. (1988) Pharmacologic marrow purging in murine T cell leukemia. Blood 71:1656-61